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Study on the expressions of PHD and HIF in placentas from normal pregnant women and patients with preeclampsia.

ABSTRACT: To investigate the relationship between oxygen sensitivity of trophoblast and hypoxia in preeclamptic placenta by the study on the expressions of hypoxia-inducible factor prolyl 4-hydroxylase (PHD) and hypoxia-inducible factor (HIF) in placentas from normal pregnant women and patients with pre-eclampsia.Subjects were chosen from the in-patients or the out-patients from May 2003 to May 2004. They were divided into 5 groups: early pregnancy group (EP), 13 cases; middle pregnancy group (MP), 9 cases; late pregnancy group (LP, or control group), 12 cases; preeclampsia (PE) group, 20 cases; gestational hypertension group (GH), 10 cases. The mRNA expressions of PHD-1 and -2 and -3 in placentas from all the subjects were assessed by in situ hybridization and Real-time PCR. The expressions of HIF-1? and -2? in placentas from different groups were assessed by immunohistochemistry and western blot.PHD-1,-2 and -3 mRNA were mainly expressed in cytoplasm of trophoblast, especially strongly expressed in extravillous trophoblast. During the progress of pregnancy, the expression of PHD-1 increased significantly (R=0.616, P<0.001). The PHD-1mRNA expression in placentas from PE group decreased significantly compared with that from control group, P<0.05. A significant direct correlation between the PHD-1 mRNA expression in placentas from PE group and their placenta weight was found (R=0.457, P<0.05). The HIF-2?, not the HIF-1? expression, from PE group was significantly higher than that from control group, P<0.01; The HIF-2? expression in trophoblast from PE was inversely correlated to the date of the onset of the disease (R=-0.730, P<0.01).PHD-1 played an important role in hypoxic response pathway of trophoblast through modulating the level of HIF-2?. The overly activated hypoxic response pathway of trophoblast in preeclamptic placenta, which is manifested as the result of HIF-2? over-expression, is the key point to hypoxic dysfunction of trophoblast.

SUBMITTER: Liu W

PROVIDER: S-EPMC3957083 | biostudies-other | 2014

REPOSITORIES: biostudies-other

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Study on the expressions of PHD and HIF in placentas from normal pregnant women and patients with preeclampsia.

Liu Wei W Wang Shu-Jun SJ Lin Qi-De QD

International journal of biological sciences 20140221 3

<h4>Objective</h4>To investigate the relationship between oxygen sensitivity of trophoblast and hypoxia in preeclamptic placenta by the study on the expressions of hypoxia-inducible factor prolyl 4-hydroxylase (PHD) and hypoxia-inducible factor (HIF) in placentas from normal pregnant women and patients with pre-eclampsia.<h4>Methods</h4>Subjects were chosen from the in-patients or the out-patients from May 2003 to May 2004. They were divided into 5 groups: early pregnancy group (EP), 13 cases; m ...[more]

PMID: 24644426

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Project description:BackgroundThe prone position is rarely used in medical settings in pregnancy. There is no published information about the prone position in women with preeclampsia. This study examined the feasibility and acceptability of the prone position in pregnant women, and the short-term effect of the prone position on blood pressure (BP) in term healthy pregnant women and in women with preeclampsia.MethodsAfter ethics approval, written consent and trial registration (ACTRN:12615000160538 registered 18/02/2015, date of first participant enrolled 03/03/2015), 50 healthy term pregnant women and 15 women with preeclampsia had BP, heart rate (HR), oxygen saturation (SpO2), respiratory rate (RR), fetal heart rate (FHR) and comfort levels measured in two positions: left lateral, and prone. Measurements were after five minutes rest in each position.ResultsMean?±?SD age, gestation and body mass index for healthy pregnant women was 33?±?4.1 years, 38?±?1.0 weeks and 27?±?3.2 kg.m-?2 and for women with preeclampsia was 32?±?4.7 years, 36?±?3.4 weeks, 31?±?5.6 kg.m-?2 respectively. No clinically significant changes occurred in healthy pregnant women in the prone position. Systolic BP was reduced in the prone position in women with preeclampsia (P?=?0.019, mean difference?-?6.6 mmHg, 95% confidence interval?-?11.9 to -?1.3 mmHg). 33% of women with preeclampsia experienced a 10 mmHg or greater reduction in systolic BP in the prone position. 42% of healthy pregnant women and 47% of women with preeclampsia preferred the prone position to lateral.ConclusionsThis is the first study to examine the prone position in women with preeclampsia. For short periods of time the prone position is feasible and comfortable in pregnant women including those at term. The prone position may reduce systolic BP in women with preeclampsia without obvious adverse effects. Larger studies with women lying for longer periods in the prone position are required. Pregnancy should not be a contraindication to the prone position for short periods of time.Trial registrationACTRN:12615000160538.

Project description:BackgroundPreeclampsia is a pregnancy-specific disorder that remains a leading cause of maternal, fetal and neonatal morbidity and mortality, and is associated with risk for future cardiovascular disease. There are no reliable predictors, specific preventative measures or treatments other than delivery. A widely held view is that the antecedents of preeclampsia lie with impaired placentation in early pregnancy. Accordingly, we hypothesized dysregulation of global gene expression in first trimester placentas of women who later manifested preeclampsia.MethodsSurplus chorionic villus sampling (CVS) tissues were collected at 10-12 weeks gestation in 160 patients with singleton fetuses. Four patients developed preeclampsia, and their banked CVS specimens were matched to 8 control samples from patients with unaffected pregnancies. Affymetrix HG-U133 Plus 2.0 GeneChips were utilized for microarray analysis. Naïve Bayes prediction modeling and pathway analysis were conducted. qRT-PCR examined three of the dysregulated genes.ResultsThirty-six differentially expressed genes were identified in the preeclampsia placentas. qRT-PCR verified the microarray analysis. Thirty-one genes were down-regulated. Many were related to inflammation/immunoregulation and cell motility. Decidual gene dysregulation was prominent. No evidence was found for alterations in hypoxia and oxidative stress regulated genes.ConclusionsTo our knowledge, this is the first study to show dysregulation of gene expression in the early placentas of women approximately 6 months before developing preeclampsia, thereby reinforcing a placental origin of the disorder. We hypothesize that placentation in preeclampsia is compromised in the first trimester by maternal and fetal immune dysregulation, abnormal decidualization, or both, thereby impairing trophoblast invasion. Several of the genes provide potential targets for the development of clinical biomarkers in maternal blood during the first trimester. Supplementary materials are available for this article via the publisher's online edition.

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Study on the expressions of PHD and HIF in placentas from normal pregnant women and patients with preeclampsia.

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Study on the expressions of PHD and HIF in placentas from normal pregnant women and patients with preeclampsia.

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